Antiproliferative Effect of a Synthetic Aptamer Mimicking Androgen Response Elements in the Lncap Cell Line Publisher Pubmed



Kouhpayeh S¹ ; Einizadeh AR² ; Hejazi Z³ ; Boshtam M⁴ ; Shariati L³ ; Mirian M³ ; Darzi L³ ; Sojoudi M² ; Khanahmad H^{3, 5} ; Rezaei A¹ Show Affiliations
Source: Cancer Gene Therapy Published:2016

Abstract

Prostate cancer usually develops to a hormone-refractory state that is irresponsive to conventional therapeutic approaches. Therefore, new methods for treating aggressive prostate cancer are under development. Because of the importance of androgen receptors (ARs) in the development of the hormone-refractory state and AR mechanism of action, this study was designed. A single-stranded DNA as an aptamer was designed that could mimic the hormone response element (HRE). The LNCaP cells as an AR-rich model were divided into three sets of triplicate groups: the test group was transfected with Aptamer Mimicking HRE (AMH), Mock received only transfection reagents (mock) and a negative control. All three sets received 0, 10 and 100 nM of dehydroepiandrosterone (DHEA) separately. Data analysis showed hormone dependency of LNCaP cells in the negative control group upon treatment with 10 and 100 nM DHEA (compared with cells left untreated (P=0.001)). Transfection of AMH resulted in significant reduction of proliferation in the test group when compared with the negative control group with 10 (P=0.001) or 100 nM DHEA (P=0.02). AMH can form a hairpin structure at 37 °C and mimic the genomic HRE. Hence, it is capable of effectively competing with genomic HRE and interrupting the androgen signaling pathway in a prostate cancer cell line (LNCaP). © 2016 Nature America, Inc., part of Springer Nature.